Sodium hydride → 2-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-4-iodo-pyridine-3-carbaldehyde

HRID 337288

反応式

HRID 337288 の反応式
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[NH:10][N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].F[C:19]1[N:26]=[CH:25][CH:24]=[C:23]([I:27])[C:20]=1[CH:21]=[O:22].[NH4+].[Cl-]>C1COCC1.O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:19]1[C:20]([CH:21]=[O:22])=[C:23]([I:27])[CH:24]=[CH:25][N:26]=1)[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

参加物

7

反応物 4

HCID 24758Sodium hydride2 回HCID 25517Ammonium ChlorideHCID 99923282-Fluoro-4-iodopyridine-3-carbaldehydeHCID 576339336-(tert-butyl)phthalazin-1(2H)-one

生成物 1

HCID 866769322-(6-tert-Butyl-1-oxo-1H-phthalazin-2-yl)-4-iodo-pyridine-3-carbaldehyde

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

In a 100 mL round-bottomed flask, 6-tert-butylphthalazin-1(2H)-one (700 mg, 3.46 mmol, Eq: 1.00) was combined with THF (30 ml) to give a colorless solution. Sodium hydride (152 mg, 3.81 mmol, Eq: 1.1) was added. The reaction mixture was stirred at ambient temperature for 15 min. A solution of 2-fluoro-4-iodonicotinaldehyde (956 mg, 3.81 mmol, Eq: 1.1) in 10 mL THF was the added to the reaction mixture and it was stirred at ambient temperature for 3.5 h. The reaction was not complete. An additional 50 mg NaH was added. The reaction was stirred for an additional 1.5 h, before addition of saturated NH4Cl. The reaction mixture was poured into 100 mL H2O and extracted with dichloromethane (5×50 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 80 g, 10% to 60% EtOAc in hexanes) to afford slightly impure product. The product was triturated with EtOAc to afford the desired product as a cream solid. The combined filtrate and washes from the trituration were concentrated, re-purified by flash chromatography (silica gel, 80 g, 10% to 60% EtOAc in hexanes) and trituration with EtOAc to afford additional product as a cream solid. The two batches of product were combined to afford 320 mg of the desired product. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.44 (s, 9 H) 7.74 (d, J=1.89 Hz, 1 H) 7.89 (dd, J=8.50, 1.70 Hz, 1 H) 8.02 (d, J=5.29 Hz, 1 H) 8.28-8.44 (m, 3 H) 9.92 (s, 1 H) (M+H)+=434 m/e.

後処理

  1. customto give a colorless solution
  2. additionadded to the reaction mixture and it
  3. stirringwas stirred at ambient temperature for 3.5 h
  4. extractionextracted with dichloromethane (5×50 mL)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 80 g, 10% to 60% EtOAc in hexanes)
  8. customto afford slightly impure product
  9. customThe product was triturated with EtOAc

出典と根拠

ORDレコード
ord-4713877f991d4b7397b76c3546b6bc48
出典データセット
uspto-grants-2014_11
特許番号
US08889682B2

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